Isolation of a partial candidate gene for Menkes disease by positional cloning

Nat Genet. 1993 Jan;3(1):20-5. doi: 10.1038/ng0193-20.


Menkes disease is an X-linked recessive disorder of copper metabolism resulting in death in early infancy. The gene has been mapped to band Xq13 based, in part, on a translocation breakpoint in a female with the disease, which was found to lie within 300 kilobases (kb) of the PGK-1 locus, allowing the isolation of a YAC clone spanning the breakpoint. Phage subclones from the breakpoint region were isolated and used to screen cDNA libraries. cDNA clones were found which detect an 8 kb transcript from normal individuals but show diminished or absent hybridization in Menkes disease patients. Partial sequence of the cDNA shows a unique open reading frame containing putative metal binding motifs which have been found in heavy metal resistance genes in bacteria. This gene is a strong candidate for the Menkes disease gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cation Transport Proteins*
  • Cells, Cultured
  • Chromosomes, Fungal
  • Cloning, Molecular
  • Copper-Transporting ATPases
  • DNA / isolation & purification
  • Electrophoresis, Gel, Pulsed-Field
  • Female
  • Gene Library
  • Genome, Human
  • Humans
  • Male
  • Menkes Kinky Hair Syndrome / genetics*
  • Metals / metabolism*
  • Molecular Sequence Data
  • Pedigree
  • Recombinant Fusion Proteins*
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • Translocation, Genetic


  • Carrier Proteins
  • Cation Transport Proteins
  • Metals
  • Recombinant Fusion Proteins
  • DNA
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases